Investigations into the cellular and molecular mechanisms that lead to abnormalities associated with developmental disabilities and mental retardation are increasingly being carried out with in vitro model systems such as cell cultures, including cells transfected with foreign genes and cells derived from transgenic and knockout mice. Advances in understanding the mechanisms for the biochemical pathology of diseases that lead to mental retardation, such as Down syndrome or the mucopolysaccharidoses, have been critically dependent upon the development of techniques for studying the altered cellular and biochemical milieu in isolated cell culture systems. In addition, state-of- the-art research in developmental biology frequently requires that investigators develop unique biological reagents such as polyclonal and monoclonal antibodies, various types of nucleotide probes, and constructs for transfection of foreign genes into cells. The Tissue Culture/Monoclonal Antibodies Laboratory (TCMAC) has facilitated the research of several of the Kansas MRDDRC investigators by providing core facilities and services that enable them to develop, maintain, and characterize numerous cellular model systems for exploring aspects of normal cell growth, signaling pathways that regulate cell viability, and effects of exogenous agents that enhance or disrupt cell growth. The TCMAC Laboratory takes great pride in the many enhancements that have been made in the facility during the past grant period as these improvements enable the lab to provide the highest level of support for MRDDRC investigators. The facility has also successfully developed unique polyclonal and monoclonal antibodies that served the needs of individual investigators. The antibody work done for Robert Palazzo has provided an excellent tool in his efforts to identify critical proteins in the centrosome and monitor changes during the cell cycle. The series of antibodies developed for Elias Michaelis have led to important discoveries regarding protein expression and localization in response to chronic ethanol exposure. Antibodies developed by the facility during the past grant period are currently being utilized at other universities in collaborative studies, and a major company has expressed interested in marketing some of those highly specific and valuable tools so they will be available to scientists on an international level. As the TCMAC looks to the future and means of enhancing the Center's focus on biobehavioral processes, the Core will play an expanding role in studies involving gene transfections, growth of ES cells, and other techniques required to produce transgenic or knockout mice. The TCMAC has been and continues to be a relatively small core, but it has played an extremely important role in attracting new, highly productive scientists to the Center itself and encouraging them to apply their talents to new, highly productive scientists to the Center itself and encouraging them to apply their talents to question related to developmental disabilities. For example, the TCMAC was instrumental in the attracting Rick Dobrowsky, Doug Ruden and Robert Palazzo to the MRDDRC shortly after they joined to KU faculty. This core is likely to continue in this role as the University hires new faculty members in the areas of molecular genetics, bioinformatics and developmental neurobiology. The goal of the TCMAC has been and will continue to be the provision of unique bioreagents, skilled technical support, and state-of-the-art equipment to facilitate and enhance the research of MRDDRC investigators who study molecular events leading to developmental disabilities. The TCMAC will continue to facilitate MRDDRC research at The University of Kansas by: (1) Maintaining a centralized facility that provides a cost-effective alternative to purchase of expensive equipment and services by MRDDRC investigators. (2) Producing and characterizing unique monoclonal/polyclonal antibodies and maintaining hybridoma cell lines for projects requiring a consistent supply of antibodies.